An experimentally-validated numerical model of diffusion and speciation of water in rhyolitic silicate melt

The diffusion of water through silicate melts is a key process in volcanic systems. Diffusion controls the growth of the bubbles that drive volcanic eruptions and determines the evolution of the spatial distribution of dissolved water during and after magma mingling, crystal growth, fracturing and fragmentation, and welding of pyroclasts. Accurate models for water diffusion are therefore essential for forward modelling of eruptive behaviour, and for inverse modelling to reconstruct eruptive and post-eruptive history from the spatial distribution of water in eruptive products. Existing models do not include the kinetics of the homogeneous species reaction that interconverts molecular () and hydroxyl () water; reaction kinetics are important because final species distribution depends on cooling history. Here we develop a flexible 1D numerical model for diffusion and speciation of water in silicate melts. We validate the model against FTIR transects of the spatial distribution of molecular, hydroxyl, and total water across diffusion-couple experiments of haplogranite composition, run at 800–1200°C and 5 kbar. We adopt a stepwise approach to analysing and modelling the data. First, we use the analytical Sauer-Freise method to determine the effective diffusivity of total water as a function of dissolved water concentration and temperature for each experiment and find that the dependence of on is linear for wt.% and exponential for wt.%. Second, we develop a 1D numerical forward model, using the method of lines, to determine a piece-wise function for that is globally-minimized against the entire experimental dataset. Third, we extend this numerical model to account for speciation of water and determine globally-minimized functions for diffusivity of molecular water and the equilibrium constant for the speciation reaction. Our approach includes three key novelties: 1) functions for diffusivities of and , and the speciation reaction, are minimized simultaneously against a large experimental dataset, covering a wide range of water concentration ( wt.%) and temperature (), such that the resulting functions are both mutually-consistent and broadly applicable; 2) the minimization allows rigorous and robust analysis of uncertainties such that the accuracy of the functions is quantified; 3) the model can be straightforwardly used to determine functions for diffusivity and speciation for other melt compositions pending suitable diffusion-couple experiments. The modelling approach is suitable for both forward and inverse modelling of diffusion processes in silicate melts; the model is available as a Matlab script from the electronic supplementary material

Functional Characterization of Circulating Tumor Cells with a Prostate-Cancer-Specific Microfluidic Device

Cancer metastasis accounts for the majority of cancer-related deaths owing to poor response to anticancer therapies. Molecular understanding of metastasis-associated drug resistance remains elusive due to the scarcity of available tumor tissue. Isolation of circulating tumor cells (CTCs) from the peripheral blood of patients has emerged as a valid alternative source of tumor tissue that can be subjected to molecular characterization. However, issues with low purity and sensitivity have impeded adoption to clinical practice. Here we report a novel method to capture and molecularly characterize CTCs isolated from castrate-resistant prostate cancer patients (CRPC) receiving taxane chemotherapy. We have developed a geometrically enhanced differential immunocapture (GEDI) microfluidic device that combines an anti-prostate specific membrane antigen (PSMA) antibody with a 3D geometry that captures CTCs while minimizing nonspecific leukocyte adhesion. Enumeration of GEDI-captured CTCs (defined as intact, nucleated PSMA+/CD45− cells) revealed a median of 54 cells per ml identified in CRPC patients versus 3 in healthy donors. Direct comparison with the commercially available CellSearch® revealed a 2–400 fold higher sensitivity achieved with the GEDI device. Confocal microscopy of patient-derived GEDI-captured CTCs identified the TMPRSS2:ERG fusion protein, while sequencing identified specific androgen receptor point mutation (T868A) in blood samples spiked with only 50 PC C4-2 cells. On-chip treatment of patient-derived CTCs with docetaxel and paclitaxel allowed monitoring of drug-target engagement by means of microtubule bundling. CTCs isolated from docetaxel-resistant CRPC patients did not show any evidence of drug activity. These measurements constitute the first functional assays of drug-target engagement in living circulating tumor cells and therefore have the potential to enable longitudinal monitoring of target response and inform the development of new anticancer agents

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

Permeability of packs of polydisperse hard spheres

The permeability of packs of spheres is important in a wide range of physical scenarios. Here, we create numerically generated random periodic domains of spheres that are polydisperse in size and use lattice-Boltzmann simulations of fluid flow to determine the permeability of the pore phase interstitial to the spheres. We control the polydispersivity of the sphere size distribution and the porosity across the full range from high porosity to a close packing of spheres. We find that all results scale with a Stokes permeability adapted for polydisperse sphere sizes. We show that our determination of the permeability of random distributions of spheres is well approximated by models for cubic arrays of spheres at porosities greater than ∼0.38, without any fitting parameters. Below this value, the Kozeny-Carman relationship provides a good approximation for dense, closely packed sphere packs across all polydispersivity

Experimental sintering of ash at conduit conditions and implications for the longevity of tuffisites

Escape of gas from magma in the conduit plays a crucial role in mitigating explosivity. Tuffisite veins—ash-filled cracks that form in and around volcanic conduits—represent important gas escape pathways. Sintering of the ash infill decreases its porosity, eventually forming dense glass that is impermeable to gas. We present an experimental investigation of surface tension-driven sintering and associated densification of rhyolitic ash under shallow conduit conditions. Suites of isothermal (700–800 °C) and isobaric H2O pressure (20 and 40 MPa) experiments were run for durations of 5–90 min. Obsidian powders with two different size distributions were used: 1–1600 μm (mean size = 89 μm), and 63–400 μm (mean size = 185 μm). All samples evolved similarly through four textural phases: phase 1—loose and cohesion-less particles; phase 2—particles sintered at contacts and surrounded by fully connected tortuous pore space of up to ~40% porosity; phase 3—continuous matrix of partially coalesced particles that contain both isolated spherical vesicles and connected networks of larger, contorted vesicles; phase 4—dense glass with 2–5% fully isolated vesicles that are mainly spherical. Textures evolve faster at higher temperature and higher H2O pressure. Coarse samples sinter more slowly and contain fewer, larger vesicles when fully sintered. We quantify the sintering progress by measuring porosity as a function of experimental run-time, and find an excellent collapse of data when run-time is normalized by the sintering timescale λs ¼ ηR=σ, where η is melt viscosity, R is mean particle radius, and σ is melt–gas surface tension. Because timescales of diffusive H2O equilibration are generally fast compared to those of sintering, the relevant melt viscosity is calculated from the solubility H2O content at experimental temperature and pressure. We use our results to develop a framework for estimating ash sintering rates under shallow conduit conditions, and predict that sintering of ash to dense glass can seal tuffisites in minutes to hours, depending on pressure (i.e., depth), temperature, and ash size

Experimental constraints on the textures and origin of obsidian pyroclasts

Obsidian pyroclasts are commonly preserved in the fall deposits of explosive silicic eruptions. Recent work has suggested that they form by sintering of ash particles on the conduit walls above the fragmentation depth and are subsequently torn out and transported in the gas-particle dispersion. Although the sintering hypothesis is consistent with the general vesicle textures and dissolved volatiles in obsidian pyroclasts, previous sintering experiments do not capture all of the textural complexities observed in the natural pyroclasts. Here, we design experiments in which unimodal and bimodal distributions of rhyolitic ash are sintered at temperatures and H2O pressures relevant to shallow volcanic conduits and under variable cooling rates. The experiments produce dense, welded obsidian that have a range of textures similar to those observed in natural pyroclasts. We find that using a unimodal distribution of particles produces obsidian with evenly distributed trapped vesicles, while a bimodal initial particle distribution produces obsidian with domains of poorly vesicular glass among domains of more vesicle-rich glass. We also find that slow cooling leads to resorption of trapped vesicles, producing fully dense obsidian. These broad features match those found in obsidian pyroclasts from the North Mono (California, USA) rhyolite eruption, providing strong support to the hypothesis that obsidian can be produced by ash sintering above the fragmentation depth during explosive eruptions

Volatile budgets and evolution in porphyry-related magma systems, determined using apatite

Volatile-bearing minerals, such as apatite, Ca5(PO4)3(OH,F,Cl), can record changes in dissolved magmatic volatile species during differentiation and, unlike melt inclusions, are sensitive to the presence of an exsolved fluid phase. Populations of apatite crystals from an individual sample can therefore be used to define the progressive volatile evolution of melt ± fluid during magma differentiation. Despite the importance of fluid chemistry in mineralisation processes, this approach remains relatively underdeveloped for porphyry mineralisation scenarios. Here, we present a model, including a standalone MATLAB app, for melt + apatite ± fluid fractionation that incorporates non-ideal, temperature-dependent KDs for OH-Cl-F exchange and permits an analysis of uncertainty arising from non-unique parameter combinations. We apply the model to apatite from the Fe-Cu-Au Corrocohuayco porphyry-skarn system and analyse differences in volatile saturation state and fluid salinity between different units. We find that there is little difference in the overall fluid salinity, and thus the fluid copper loads, but that the more primitive unit (i.e. the gabbrodiorites) reached fluid saturation much later (after around 50% crystallisation) than the more evolved units, implying that the melt volatile concentration recorded by the apatites in the gabbrodiorites is not representative of the initial magma volatile budget. This work demonstrates that apatite can be a good alternative means of reconstructing the evolving magmatic fluid salinity within mineralising systems, and linking this to the trace metal content of the melt

Rapid pre-eruptive mush reorganisation and atmospheric volatile emissions from the 12.9 ka Laacher See eruption, determined using apatite

Magma is commonly thought to be stored as a crystal-rich mush within vertically extensive, crustal storage regions. A key unknown is how to remobilise and erupt such crystal-rich material, and whether the growth of gas bubbles within the mush could promote remobilisation. In order to investigate this, we need improved constraints on the timing of volatile saturation in magmas. The mineral apatite represents a potentially useful record of pre-eruptive magmatic volatiles, but data interpretation is complex because exchange reactions control the volatile partitioning. Model solutions are therefore non-unique. Here, we present a numerical forward modelling program with a sensitivity analysis function, which addresses non-uniqueness by identifying alternative sets of starting parameters that match a target compositional trend through a population of apatite crystals. The model is applied to a new dataset of volatiles in apatite from the 12.9 ka Laacher See eruption, Eifel volcanic region, Germany. The results indicate that the magma was initially strongly volatile-undersaturated and became saturated through progressive crystal fractionation. Apatite crystals are not in volatile or trace element equilibrium with their carrier melts, indicating dispersal of crystals into different chemical environments. Consideration of apatite diffusivities suggests that this reorganisation occurred shortly before eruption. Our modelling results also allow us to constrain directly the amount of pre-eruptive magmatic vapour emitted during the explosive eruption, highlighting the importance of considering the behaviour of halogens during magma storage. Overall, our approach confirms the value of measuring apatite volatile contents and highlights the potential of this method to provide quantitative constraints on magmatic evolution and storage conditions